5,7-Dimethoxy-3-(3-chlorophenyl)-4H-1-benzopyran-4-one | 59108-74-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 5,7-Dimethoxy-3-(3-chlorophenyl)-4H-1-benzopyran-4-one
• 英文别名: 3-(3-Chlorophenyl)-5,7-dimethoxychromen-4-one
• CAS: 59108-74-6
• 化学式: C₁₇H₁₃ClO₄
• 分子量: 316.741
• InChiKey: USNKYQXLHXAMIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  重氮甲烷 、 3-(3-Chloro-phenyl)-5,7-dihydroxy-chromen-4-one 在 甲醇 作用下， 反应 96.0h， 以6%的产率得到5,7-Dimethoxy-3-(3-chlorophenyl)-4H-1-benzopyran-4-one
  参考文献：
  名称：

  Use of a Pharmacophore Model for the Design of EGFR Tyrosine Kinase Inhibitors:  Isoflavones and 3-Phenyl-4(1H)-quinolones

  摘要：

  Using a pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGFR protein tyrosine kinase together with published X-ray crystal data of quercetin (2) in complex with the lick tyrosine kinase and of deschloroflavopiridol (3b) in complex with CDK2, a putative binding mode of the isoflavone genistein (1) was proposed. Then, based on literature data suggesting that a salicylic acid function, which is represented by the 5-hydroxy-4-keto motif in I, could serve as a pharmacophore replacement of a pyrimidine ring, superposition of 1 onto the potent EGFR tyrosine kinase inhibitor 4-(3'-chlorophenylamino)-6,7-dimethoxyquinazoline (4) led to 3'-chloro-5,7-clibydroxyisoflavone (fi) as a target structure which in fact was 10 times more potent than 1. The putative binding mode of 6 suggests a sulfur-aromatic interaction of the m-chlorophenyl moiety with Cys 773 in the "sugar pocket" of the EGFR kinase model. Replacement of the oxygen in the chromenone ring of 6 by a nitrogen atom further improved the inhibitory activity against the EGFR kinase. With IC50 values of 38 and 8 nM, respectively, the quinolones 11 and 12 were the most potent compounds of the series. N-Alkylation of II did not further improve enzyme inhibitory activity but; led to derivatives with cellular activity in the lower micromolar range.

  DOI：

  10.1021/jm980551o

文献信息

• Ground mixture
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0129893A2

  公开（公告）日：1985-01-02

  A ground mixture of a poorly soluble cystalline drug and an adsorbent is remarkably improved in the rates of dissolution and absorption of the drug.

  将溶解性较差的胱氨酸药物和吸附剂混合研磨后，可显著提高药物的溶解和吸收率。
• US4772627A
  申请人：——

  公开号：US4772627A

  公开（公告）日：1988-09-20
• Use of a Pharmacophore Model for the Design of EGFR Tyrosine Kinase Inhibitors:  Isoflavones and 3-Phenyl-4(1<i>H</i>)-quinolones
  作者：Peter Traxler、Jennifer Green、Helmut Mett、Urs Séquin、Pascal Furet

  DOI：10.1021/jm980551o

  日期：1999.3.1

  Using a pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGFR protein tyrosine kinase together with published X-ray crystal data of quercetin (2) in complex with the lick tyrosine kinase and of deschloroflavopiridol (3b) in complex with CDK2, a putative binding mode of the isoflavone genistein (1) was proposed. Then, based on literature data suggesting that a salicylic acid function, which is represented by the 5-hydroxy-4-keto motif in I, could serve as a pharmacophore replacement of a pyrimidine ring, superposition of 1 onto the potent EGFR tyrosine kinase inhibitor 4-(3'-chlorophenylamino)-6,7-dimethoxyquinazoline (4) led to 3'-chloro-5,7-clibydroxyisoflavone (fi) as a target structure which in fact was 10 times more potent than 1. The putative binding mode of 6 suggests a sulfur-aromatic interaction of the m-chlorophenyl moiety with Cys 773 in the "sugar pocket" of the EGFR kinase model. Replacement of the oxygen in the chromenone ring of 6 by a nitrogen atom further improved the inhibitory activity against the EGFR kinase. With IC50 values of 38 and 8 nM, respectively, the quinolones 11 and 12 were the most potent compounds of the series. N-Alkylation of II did not further improve enzyme inhibitory activity but; led to derivatives with cellular activity in the lower micromolar range.